Pediatric astrocytomas are the most common form of brain cancer in children. This POI is designed to improve our understanding ofthe pathways that regulate these tumor cells and the environment in which such cells reside, and thereby to develop new therapeufic approaches. The Innovative Neuropathology (INP) Core seeks to facilitate this research through the following specific aims: 1. To generate and characterize primary pediatric astrocytoma cell lines and fissue resources. 2. To provide expert neuropathologic and molecular pathologic analysis of human and mouse astrocytoma models. 3. To develop innovative technologies for cellular and molecular characterizafion of pediatric astrocytomas and cell lines. 4. To ensure that tumor samples are used and analyzed in a stafisfically rigorous and efficient fashion. Given that the research of each project is heavily based upon the in vivo biology of human and mouse astrocytomas, the INP Core services focus on development and delivery of in vivo technologies such as immunohistochemistry, in situ hybridization, fluorescent in situ hybridization (FISH) for genomic aberrations, and genome wide technologies for studies in human tumors. In addition, the INP Core will work to improve emerging fissue technologies to enable analysis of small tumor samples and so conserve these rare tissue resources. In time these innovafions can lead to clinical tests that identify pafients who might benefit from particular targeted therapies (e.g. BRAF expression signatures that allow rapid screening for tumor samples likely to have BRAF mutafions). The centralized nature ofthe INP Core will foster intellectual resource sharing and allow investigators to accurately compare and interpret their findings within the spectrum of research performed across all the projects. The INP Core has the requisite neuropathologic expertise, biostatisfical knowledge, sophisticated resources, and experienced staff to carry out these aims and ensure that the POI meets its overall goals to improve our understanding of pediatric astrocytomas.

Public Health Relevance

Pediatric brain tumors are one of the most common solid tumors in children. Targeted therapies are needed to both control the tumor and avoid the long term effects of current treatments. The Innovative Neuropathology Core seeks to support the Projects in discovery of the pathways that control growth of pediatric astrocytomas and in development of innovafive genefic technologies that can identify particular patients who might benefit from therapies against these pathways.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-O)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dana-Farber Cancer Institute
United States
Zip Code
Filbin, Mariella G; Tirosh, Itay; Hovestadt, Volker et al. (2018) Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science 360:331-335
Ramkissoon, Shakti H; Bandopadhayay, Pratiti; Hwang, Jaeho et al. (2017) Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: precision medicine analysis of 203 pediatric brain tumors. Neuro Oncol 19:986-996
Sun, Yu; Alberta, John A; Pilarz, Catherine et al. (2017) A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. Neuro Oncol 19:774-785
Zhao, Xuesong; Pak, Ekaterina; Ornell, Kimberly J et al. (2017) A Transposon Screen Identifies Loss of Primary Cilia as a Mechanism of Resistance to SMO Inhibitors. Cancer Discov 7:1436-1449
Ni, Jing; Xie, Shaozhen; Ramkissoon, Shakti H et al. (2017) Tyrosine receptor kinase B is a drug target in astrocytomas. Neuro Oncol 19:22-30
Ilic, Nina; Birsoy, K?vanç; Aguirre, Andrew J et al. (2017) PIK3CA mutant tumors depend on oxoglutarate dehydrogenase. Proc Natl Acad Sci U S A 114:E3434-E3443
Zhou, Jing; Tien, An-Chi; Alberta, John A et al. (2017) A Sequentially Priming Phosphorylation Cascade Activates the Gliomagenic Transcription Factor Olig2. Cell Rep 18:3167-3177
Zhang, Jing; Gao, Xueliang; Schmit, Fabienne et al. (2017) CRKL Mediates p110?-Dependent PI3K Signaling in PTEN-Deficient Cancer Cells. Cell Rep 20:549-557
Pak, Ekaterina; Segal, Rosalind A (2016) Hedgehog Signal Transduction: Key Players, Oncogenic Drivers, and Cancer Therapy. Dev Cell 38:333-44
Stevens, Mark M; Maire, Cecile L; Chou, Nigel et al. (2016) Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate. Nat Biotechnol 34:1161-1167

Showing the most recent 10 out of 59 publications